Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma concentrations of atrial natriuretic factor and some vasoactive substances were determined in 8 patients with aldosterone-producing adenoma, 10 with idiopathic adrenal hyperplasia, 10 normotensive subjects and 12 patients with essential hypertension. Plasma atrial natriuretic factor concentration in patients with aldosterone-producing adenoma was the highest among the examined groups. Adrenal surgery reduced plasma concentrations of atrial natriuretic factor and aldosterone concomitant with the elevation in urinary sodium excretion, plasma renin activity and urinary sodium-to-potassium ratio. Withdrawal of trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor) in patients with idiopathic adrenal hyperplasia increased plasma concentrations of atrial natriuretic factor and aldosterone, and decreased the urinary sodium-to-potassium ratio, plasma renin activity and urinary sodium excretion. However, reduced urinary sodium excretion following trilostane treatment returned to the control level successively despite the high levels of plasma atrial natriuretic factor and aldosterone. Acute infusion of saline remarkably increased plasma atrial natriuretic factor concentration in patients with idiopathic adrenal hyperplasia and aldosterone-producing adenoma. These results suggest that a high level of atrial natriuretic factor is a characteristic feature in patients with aldosterone-producing adenoma caused chiefly by the expansion of extracellular fluid volume, and circulating atrial natriuretic factor may contribute to regulation of the sodium escape phenomenon in patients with aldosterone-producing adenoma or idiopathic adrenal hyperplasia.
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PMID:The effect of adrenal surgery on plasma atrial natriuretic factor and sodium escape phenomenon in patients with primary aldosteronism. 252 99

Adrenal and gonadal functions were evaluated on two adult cousins with male pseudohermaphroditism due to congenital 3 beta-hydroxysteroid dehydrogenase deficiency (3 beta-HSD) without clinical salt-losing. Both patients had been reared as females since birth. Case 1 presented at age 17 with perineal hypospadias virilization without gynecomastia and a female to male gender role change at puberty. Case 2 had previously undergone bilateral orchidectomy in childhood and presented "primary amenorrhea", absence of virilization and a female gender role at the age of 24. In the basal state, as well as after ACTH and hCG stimulation, 3 beta-hydroxy-5-ene-steroid levels were disproportionately elevated, resulting in abnormal 3 beta-hydroxy-5-ene: 3-oxi-4-ene steroids ratios. Normal basal serum cortisol with inadequate cortisol response to ACTH was observed in both patients. Elevated basal plasma renin activity (PRA) and normal basal serum aldosterone (ALDO) were present in both subjects. After ACTH stimulation serum ALDO rose adequately in Case 1 but subnormally in Case 2. Salt restriction resulted in an increase in serum ALDO and no salt loss in Case 1 whereas in Case 2 the substantial rise in PRA and serum ALDO were unable to prevent slight urinary sodium loss. Case 1 had normal basal serum testosterone with subnormal response to hCG stimulation. Incubation of testicular tissue in vitro with [3H]DHEA resulted in large Androstenediol production but diminished testosterone conversion confirming the 3 beta-HSD deficiency in the testes. We conclude that (1) absence of gynecomastia and a female to male gender role change may be observed in the male pubertal presentation of nonsalt-losing 3 beta-HSD deficiency and (2) the different functional behavior of zona glomerulosa in our patients suggests the presence of variable degrees of 3 beta-HSD deficiency in the zona glomerulosa of the nonsalt-losing form.
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PMID:Male pseudohermaphroditism due to nonsalt-losing 3 beta-hydroxysteroid dehydrogenase deficiency: gender role change and absence of gynecomastia at puberty. 282 19

Trilostan (240, 360 and 480 mg/day administered p.o. to healthy men) induced an increase (P less than 0.05) in the urinary excretion rates of DHEA, androstenediol and pregnenolone but failed to influence the excretion rates of cortisol, aldosterone, and of the four glucocorticoid metabolites, THF, allo-THF, THE and allo-THE. A rise in plasma renin concentrations was seen in the initial phase of the trial. Administration of dexamethasone in addition to trilostan suppressed plasma and urinary concentrations of cortisol and the excretion rates of all estimated steroid metabolites but did not modify the relative abundance in the excretion rates of DHEA, androstenediol and pregnenolone. These results confirm that trilostan interferes with the activity of 3 beta-hydroxysteroid dehydrogenase in man. However, under physiological conditions production of cortisol and aldosterone is kept at a constant level, most likely by compensatory stimulation of the secretion of ACTH and renin.
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PMID:Effect of trilostan on steroid excretion in man: compensated inhibition of 3 beta-hydroxysteroid dehydrogenase. 293 98

In studies of a 6-yr-old boy and his non-HLA identical 8-yr-old sister, we demonstrated 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency in the biosynthetic pathways of glucocorticoids and androgens, but not mineralocorticoids. The sister did not manifest abnormal genital development at birth, but developed premature adrenarche at the age of 4 yr, with clitoromegaly and advanced bone age. The brother had perineal hypospadias at birth and developed premature adrenarche at the age of 6 yr. In both siblings, baseline and ACTH-stimulated delta 5 steroids were markedly elevated. The baseline and ACTH-stimulated ratios of delta 5 to delta 4 steroids remained extremely high, and all steroids promptly suppressed with dexamethasone (DEX). Normal baseline PRA and serum and urinary aldosterone (Aldo) levels increased after stimulation with a low Na+ diet. Renal Na+ conservation was normal after dietary Na+ deprivation with and without DEX administration. The PRA to pH 1 Aldo ratio remained normal with normal and low Na+ diets, regardless of DEX administration, indicating normal glomerulosa function with renin stimulation. In both siblings, ACTH increased PRA and Aldo levels, maintaining the PRA to pH 1 Aldo ratio unchanged from the baseline value. In contrast, in control children, PRA was suppressed, while Aldo increased, resulting in a fall of the PRA to pH 1 Aldo ratio. The increase in PRA with exogenous ACTH in these siblings suggests there may be an ACTH-stimulable mineralocorticoid antagonist. During prolonged DEX administration, hCG administration caused a slight increase in 17-hydroxypregnenolone and dehydroepiandrosterone in both the siblings, while testosterone (T) rose poorly in the brother, and estradiol did not rise at all in the sister. These results suggest the possibility of a deficiency of 3 beta-HSD in the gonads as well as the adrenals. After [3H]dehydroepiandrosterone iv infusion, there was normal conversion to [3H]-conjugated testosterone glucuronide, suggesting the presence of normal peripheral 3 beta-HSD activity. We propose that in these siblings, there is a deficiency of 3 beta-HSD in the adrenal zona fasciculata and zona reticularis, whereas 3 beta-HSD activity is intact in the zona glomerulosa. In addition, in these siblings, 3 beta-HSD deficiency was present in the gonads, while peripheral 3 beta-HSD activity appeared to be intact. These cases demonstrate further the heterogeneity of congenital adrenal hyperplasia due to 3 beta-HSD deficiency.
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PMID:Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function. 630 Jan 66

(2 alpha, 4 alpha, 5 alpha, 17 beta)-4, 5-[Epoxy-17-hydroxy-3-oxo-androstane-2-carbonitrile (Trilostane, Win 24450) is a new, orally active, competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase currently being introduced into therapy of Cushing's disease and primary aldosteronism and being investigated in the treatment of low-renin essential hypertension. In adult male rats and in healthy, young, male volunteers the effect of trilostane on testosterone production was studied. Rats were treated with trilostane 150 mg or 300 mg/kg/d for 7 or 14 days. Testosterone in serum was measured by radioimmunoassay, testes were weighed and Leydig cell nuclear volume determined. In healthy volunteers, dehydroepiandrosterone sulphate (DHEAS) and responses of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone to luteinizing hormone releasing hormone (LHRH) stimulation were measured by radioimmunoassay before and during trilostane treatment (240 mg/d). In rats, trilostane treatment decreases testosterone and increases Leydig cell nuclear volumes without affecting testicular weight. In volunteers, basal testosterone is not changed during trilostane treatment but testosterone response to LHRH is impaired. DHEAS increases. LH or FSH levels are not altered. It is concluded that trilostane treatment may decrease testosterone synthesis.
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PMID:The inhibiting effect of trilostane on testosterone synthesis. Hormonal and morphologic alterations induced by subchronic trilostane treatment in rats and healthy volunteers. 640 30

An aldosterone-producing adenoma (APA) was associated with chronic renal failure. Following treatment with Trilostane (a 3 beta-hydroxysteroid dehydrogenase inhibitor), furosemide and continuous ambulatory peritoneal dialysis (CAPD), a left adrenal adenoma was successfully removed. This patient, still being treated with CAPD, is a unique example of primary aldosteronism without showing suppressed plasma renin activity.
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PMID:Primary aldosteronism associated with chronic renal failure. Report of a case. 646 82

In adult male rats the effect of a subchronic treatment with trilostane, a new, orally active, competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase, on adrenal steroid production and morphology was studied. Rats were treated with 150 mg or 300 mg trilostane/kg/day for 7 or 14 days and with 150 mg trilostane/kg/day for 10 days in combination with 75 mg propranolol/kg/day or 1 mg indomethacin/kg/day. Trilostane leads to a dose-dependent increase in adrenal weight and to a rather uniform increase in nuclear volumes of zona glomerulosa and zona fasciculata cells. The basal secretion of aldosterone and corticosterone is not significantly altered. Trilostane increases the excretion of sodium and potassium in urine. The stimulating effect of trilostane on plasma renin activity and the adrenal enlargement are not inhibited by propranolol or indomethacin. We conclude that trilostane induces latent adrenal insufficiency. Increased renin and ACTH maintain normal basal steroid levels, and might impair the therapeutic effectiveness of trilostane.
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PMID:The inhibiting effect of trilostane on adrenal steroid synthesis: hormonal and morphological alterations induced by subchronic trilostane treatment in normal rats. 704 68

A 5-year-old XY pseudohermaphrodite was found to have a defect of steroid biosynthesis consistent with a partial deficiency of the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Circulating concentrations of delta 5 steroids and delta 5 urinary steroid metabolites were elevated and remained elevated after orchidectomy. There was no evidence of salt loss, plasma renin being within normal limits, and no detectable glucocorticoid abnormality. The coding sequences of the genes for 3 beta-HSD types I and II were amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis (DGGE) and manual and automatic DNA sequencing. A mutation in the gene for 3 beta-HSD type II was observed at codon 173 (CTA-->CGA), leading in the affected patient to a homozygous substitution in which the leucine at residue 173 was altered to an arginine (L173R). The propositus's 2-year-old XX sister was also homozygous for L173R and showed the biochemical characteristics of partial 3 beta-HSD deficiency without clinical symptoms or signs. The mutation segregated as an autosomal recessive. Three related heterozygous adult females showed evidence of a small over-production of delta 5 steroids and steroid metabolites and a variable reduction in ovarian function. Concentrations of delta 5 steroids and steroid metabolites in the heterozygous father of the propositus were within the normal range. These data are discussed in relation to the endocrine causes of pseudohermaphroditism and hirsutism. Evidence for tight linkage between the genes for 3 beta-HSD types I and II was obtained using a microsatellite polymorphism in the third intron of the gene for 3 beta-HSD type II and synonymous and non-synonymous mutations and polymorphisms in the gene for 3 beta-HSD type I. The latter polymorphisms were located 88 bp apart at the 3' end of the type I coding sequence and could be physically resolved as haplotypes using DGGE. The application of DGGE to the analysis of mutations in members of a multigene family is discussed.
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PMID:Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss. 806 Apr 86

Studies of adrenal steroidogenesis have been facilitated by the availability of immortalized mouse adrenocortical Y-1 cells. We sought to make new, alternative mouse steroidogenic cell lines by genetically targeted tumorigenesis. Transgenic mice were constructed expressing both the SV40 T-antigen and a bacterial neomycin-resistance gene under the control of the promoter for the human P450 cholesterol side-chain cleavage (P450scc) gene, which encodes the first and rate-limiting enzyme in steroidogenesis. Two female transgenic mice expressed T-antigen in various nonsteroidogenic tissues but generated tumors only in the adrenals, suggesting adrenal tumor formation was an early event. Ovarian tissues, which, unlike the adrenal, do not make steroids in fetal or early postnatal life, did not develop tumors. Cell lines derived from the adrenal tumors were resistant to the neomycin analog G418. Clonal sublines are stable, growing easily in monolayers with a doubling time of 24-60 h. The cell lines secrete progesterone and 11-deoxycorticosterone, indicating these cells express the P450scc system, 3 beta-hydroxysteroid dehydrogenase, and 21-hydroxylase activity. However the 21-hydroxylase activity was not mediated by P450c21, as the cells lacked P450c21 mRNA. The cells did not secrete any 11-hydroxylated steroids, although they contained P450c11 beta mRNA. Both the secretion of progesterone and the abundance of P450scc mRNA increase in response to 8-bromo-cAMP, but not to ACTH or angiotensin II. In addition to expression of steroidogenic enzyme mRNAs, one cell line also expresses mouse renin-1 mRNA, making these cells useful for studies of the role of adrenal renin in regulating adrenal steroidogenesis. These findings represent an approach in transgenic mice to develop highly differentiated adrenal cell lines.
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PMID:Steroidogenic adrenocortical cell lines produced by genetically targeted tumorigenesis in transgenic mice. 815 34